Use of the epidermal growth factor receptor inhibitors gefitinib, erlotinib, afatinib, dacomitinib, and icotinib in the treatment of non-small-cell lung cancer: a systematic review

Abstract

Introduction: This systematic review addresses the use of epidermal growth factor receptor (egfr) inhibitors in three populations of advanced non-small-cell lung cancer (nsclc) patients-unselected, selected, and molecularly selected-in three treatment settings: first line, second line, and maintenance.

Methods: Ninety-six randomized controlled trials found using the medline and embase databases form the basis of this review.

Results: In the first-line setting, data about the efficacy of egfr tyrosine kinase inhibitors (tkis) compared with platinum-based chemotherapy are inconsistent. Results from studies that selected patients based on clinical characteristics are also mixed. There is high-quality evidence that an egfrtki is preferred over a platinum doublet as initial therapy for patients with an activating mutation of the EGFR gene. The egfrtkis are associated with a higher likelihood of response, longer progression-free survival, and improved quality of life. Multiple trials of second-line therapy have compared an egfrtki with chemotherapy. Meta-analysis of those data demonstrates similar progression-free and overall survival. There is consequently no preferred sequence for second-line egfrtki or second-line chemotherapy. The egfrtkis have also been evaluated as switch-maintenance therapy. No molecular marker could identify patients in whom a survival benefit was not observed; however, the magnitude of the benefit was modest.

Conclusions: Determination of EGFR mutation status is essential to making appropriate treatment decisions in patients with nsclc. Patients who are EGFR mutation-positive should be treated with an egfrtki as first-line therapy. An egfrtki is still appropriate therapy in patients who are EGFR wild-type, but the selected agent should be administered as second- or third-line therapy.

Keywords: Non-small-small cell lung cancer; egfr inhibitors; mutation status; systematic review.

FIGURE 1

(A) Meta-analysis of progression-free survival, comparing epidermal growth factor receptor inhibitors with chemotherapy in molecularly selected patients. (B) Meta-analysis of progression-free survival, comparing epidermal growth factor receptor inhibitors with chemotherapy in molecularly selected patients, including those in the IPASS and First-SIGNAL trials. SE = standard error; IV = inverse variance; CI = confidence interval.

FIGURE 2

(A) Meta-analysis of overall survival, comparing epidermal growth factor receptor inhibitors with chemotherapy in molecularly selected patients. (B) Meta-analysis of overall survival, comparing epidermal growth factor receptor inhibitors with chemotherapy in molecularly selected patients, including those in the IPASS and First-SIGNAL trials. SE = standard error; IV = inverse variance; CI = confidence interval.

FIGURE 3

(A) Meta-analysis of progression-free survival, comparing epidermal growth factor receptor inhibitors with chemotherapy in second-line unselected patients. (B) Meta-analysis of overall survival, comparing epidermal growth factor receptor inhibitors with chemotherapy in second-line unselected patients. SE = standard error; IV = inverse variance; CI = confidence interval.